Mesenchymal stromal cells from amniotic fluid are less prone to senescence compared to those obtained from bone marrow: An in vitro study

Mesenchymal stromal cells (MSCs) are considered to be an excellent source in regenerative medicine. They contain several cell subtypes, including multipotent stem cells. MSCs are of particular interest as they are currently being tested using cell and gene therapies for a number of human diseases. They represent a rare population in tissues; for this reason, they require, before being transplanted, an in vitro amplification. This process may induce replicative senescence, thus affecting differentiation and proliferative capacities. Increasing evidence suggests that MSCs from fetal tissues are significantly more plastic and grow faster than MSCs from bone marrow. Here, we compare amniotic fluid mesenchymal stromal cells (AF‐MSCs) and bone marrow mesenchymal stromal cells (BM‐MSCs) in terms of cell proliferation, surface markers, multidifferentiation potential, senescence, and DNA repair capacity. Our study shows that AF‐MSCs are less prone to senescence with respect to BM‐MSCs. Moreover, both cell models activate the same repair system after DNA damage, but AF‐MSCs are able to return to the basal condition more efficiently with respect to BM‐MSCs. Indeed, AF‐MSCs are better able to cope with genotoxic stress that may occur either during in vitro cultivation or following transplantation in patients. Our findings suggest that AF‐MSCs may represent a valid alternative to BM‐MSCs in regenerative medicine, and, of great relevance, the investigation of the mechanisms involved in DNA repair capacity of both AF‐MSCs and BM‐MSCs may pave the way to their rational use in the medical field.     

Hypothermia during Carotid Endarterectomy: A Safety Study

BackgroundCEA is associated with peri-operative risk of brain ischemia, due both to emboli production caused by manipulation of the plaque and to potentially noxious reduction of cerebral blood flow by carotid clamping. Mild hypothermia (34–35°C) is probably the most effective approach to protect brain from ischemic insult. It is therefore a substantial hypothesis that hypothermia lowers the risk of ischemic brain damage potentially associated with CEA. Purpose of the study is to test whether systemic endovascular cooling to a target of 34.5–35°C, initiated before and maintained during CEA, is feasible and safe.MethodsThe study was carried out in 7 consecutive patients referred to the Vascular Surgery Unit and judged eligible for CEA. Cooling was initiated 60–90 min before CEA, by endovascular approach (Zoll system). The target temperature was maintained during CEA, followed by passive, controlled rewarming (0.4°C/h). The whole procedure was carried out under anesthesia.ResultsAll the patients enrolled had no adverse events. Two patients exhibited a transient bradycardia (heart rate 30 beats/min). There were no significant differences in the clinical status, laboratory and physiological data measured before and after CEA.ConclusionsSystemic cooling to 34.5–35.0°C, initiated before and maintained during carotid clamping, is feasible and safe.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02629653","term_id":"NCT02629653"}}NCT02629653     

Behavioral disorders as unusual presentation of pediatric extraventricular neurocytoma: report on two cases and review of the literature

Background

Extraventricular neurocytomas (EVNs) are rare parenchymal brain tumors, distinct from central neurocytomas that are typically located within the supratentorial ventricular system. Seizures and headache represent the most common symptoms of extraventricular neurocytomas in the cerebral hemisphere both in adult and pediatric population.

Case presentation

We describe two cases of pediatric EVN with clinical onset characterized by behavioral and attention deficit/ hyperactivity disorders. The association between behavioral/attention disorders in childhood and the presence of a frontal neurocytoma has never been described before. Furthermore, inappropriate levels of inattention, hyperactivity and impulsivity are common among the neurobehavioral and developmental disorders in childhood. We reviewed 43 pediatric cases of extraventricular neurocytoma included in the PubMed database and their clinical presentation, and we never found this unusual relationship.

Conclusion

In childhood, the attention/hyperactivity disorders seem to be often over-diagnosed. When these deficits are more subtle and do not well-fit in a specific neurocognitive disorder, the clinicians should have a suspicion that they might mask the clinical features of a frontal lesion. This paper is focused on the clinical presentation of the extraventricular neurocytoma and the possible organic etiology of an attention and hyperactivity deficit.

     

Tuning genetic clocks employing DNA binding sites

Periodic oscillations play a key role in cell physiology from the cell cycle to circadian clocks. The interplay of positive and negative feedback loops among genes and proteins is ubiquitous in these networks. Often, delays in a negative feedback loop and/or degradation rates are a crucial mechanism to obtain sustained oscillations. How does nature control delays and kinetic rates in feedback networks? Known mechanisms include proper selection of the number of steps composing a feedback loop and alteration of protease activity, respectively. Here, we show that a remarkably simple means to control both delays and effective kinetic rates is the employment of DNA binding sites. We illustrate this design principle on a widely studied activator-repressor clock motif, which is ubiquitous in natural systems. By suitably employing DNA target sites for the activator and/or the repressor, one can switch the clock “on” and “off” and precisely tune its period to a desired value. Our study reveals a design principle to engineer dynamic behavior in biomolecular networks, which may be largely exploited by natural systems and employed for the rational design of synthetic circuits.     

Shape and size variation: Growth and development of the dusky grouper (Epinephelus marginatus Lowe, 1834)

Demersal fishes have complex life cycles that involve an ontogenetic change in morphology, physiology, and behavior, as their pelagic larval stages colonize benthic habitats. The developmental transition between larvae and juveniles leads to very complex processes of morphogenesis and differentiation. These processes primarily determine changes in external morphology, which is shaped by selective pressures to optimize performance for basic activities such as swimming, escape from predators, and feeding. Fishes have provided fertile grounds for ecomorphological investigations throughout ontogeny, as the role of changing morphology in inducing ontogenetic niche shifts is not always clear. In this framework, some studies have demonstrated that certain species undergo gradual changes, whereas other species experience threshold effects in their ecomorphological relationships during ontogeny. In this study, the intraspecific allometry of the dusky grouper was examined. Geometric morphometric tools were used to quantify shape changes through the development, and a modular approach was also applied to analyze the pattern of covariation between three distinct blocks (head, trunk, and tail). For this purpose, a two‐block Partial Least Square was computed. This method reveals that the pattern of changes in the overall body shape is the result of the modularized changes of these blocks. J. Morphol., 2009. © 2008 Wiley‐Liss, Inc.     

Light and shape: a contribution to demonstrate morphological differences in diurnal and nocturnal teleosts

Light intensity is an important environmental factor affecting the structure of fish assemblages during the day-night cycle. Light influences how organisms perceive their environment, modulating their intraspecific and interspecific relationships. The relationship between light intensity variations and biological cycles should be observed at the level of organismal morphology. In this study the relationship between activity rhythms, thus light intensity experienced by fish in the period of major activity and external morphology, have been investigated. The morphological traits of 97 selected fish species were compared in order to determine the existence of a common morphological plan in agreement with their diurnal or nocturnal activity rhythm. Species sorting was performed by maximizing the diversity of activity rhythm, habitat choice, ecology, and trophic habits within the same family, to assess the importance of the day-night cycle on species morphology in relation to other environmental features. The morphological characters selected for the geometric morphometric analysis were body profile and the position of mouth, eye, pelvic, pectoral, dorsal, and caudal fin. The present analysis allowed different consensus forms for nocturnal and for diurnal species to be identified. Two-block Partial Least Squares analysis was then performed for the purpose of modeling the covariation between the form and two important external variables (ecology and activity).     

Potential impacts of future land use and climate change on the Red List status of the Proteaceae in the Cape Floristic Region, South Africa

Using spatial predictions of future threats to biodiversity, we assessed for the first time the relative potential impacts of future land use and climate change on the threat status of plant species. We thus estimated how many taxa could be affected by future threats that are usually not included in current IUCN Red List assessments. Here, we computed the Red List status including future threats of 227 Proteaceae taxa endemic to the Cape Floristic Region, South Africa, and compared this with their Red List status excluding future threats. We developed eight different land use and climate change scenarios for the year 2020, providing a range of best‐ to worst‐case scenarios. Four scenarios include only the effects of future land use change, while the other four also include the impacts of projected anthropogenic climate change (HadCM2 IS92a GGa), using niche‐based models. Up to a third of the 227 Proteaceae taxa are uplisted (become more threatened) by up to three threat categories if future threats as predicted for 2020 are included, and the proportion of threatened Proteaceae taxa rises on average by 9% (range 2–16%), depending on the scenario. With increasing severity of the scenarios, the proportion of Critically Endangered taxa increases from about 1% to 7% and almost 2% of the 227 Proteaceae taxa become Extinct because of climate change. Overall, climate change has the most severe effects on the Proteaceae, but land use change also severely affects some taxa. Most of the threatened taxa occur in low‐lying coastal areas, but the proportion of threatened taxa changes considerably in inland mountain areas if future threats are included. Our approach gives important insights into how, where and when future threats could affect species persistence and can in a sense be seen as a test of the value of planned interventions for conservation.     

Osteogenic transdifferentiation of vascular smooth muscle cells isolated from spontaneously hypertensive rats and potential menaquinone-4 inhibiting effect

Vascular calcification (VC) is an active and cell-mediated process that shares many common features with osteogenesis. Knowledge demonstrates that in the presence of risk factors, such as hypertension, vascular smooth muscle cells (vSMCs) lose their contractile phenotype and transdifferentiate into osteoblastic-like cells, contributing to VC development. Recently, menaquinones (MKs), also known as Vitamin K2 family, has been revealed to play an important role in cardiovascular health by decreasing VC. However, the MKs' effects and mechanisms potentially involved in vSMCs osteoblastic transdifferentiation are still unknown. The aim of this study was to investigate the possible role of menaquinone-4 (MK-4), an isoform of MKs family, in the modulation of the vSMCs phenotype. To achieve this, vascular cells from spontaneously hypertensive rats (SHR) were used as an in vitro model of cell vascular dysfunction. vSMCs from Wistar Kyoto normotensive rats were used as control condition. The results showed that MK-4 preserves the contractile phenotype both in control and SHR-vSMCs through a γ-glutamyl carboxylase-dependent pathway, highlighting its capability to inhibit one of the mechanisms underlying VC process. Therefore, MK-4 may have an important role in the prevention of vascular dysfunction and atherosclerosis, encouraging further in-depth studies to confirm its use as a natural food supplement.